Inverse Electron-Demand Diels–Alder Reaction of <i>exo</i> -Imidazolidin-2-One Dienes with In Situ Generated 1,2-Diaza-1,3-Butadienes and α-Nitrosostyrenes

Herein, we report an efficient inverse electron-demand Diels-Alder reaction between readily accessible <i>exo</i>-2-imidazolidinone dienes and in situ generated 1,2-diaza-1,3-butadienes under mild conditions. This methodology enables the synthesis of a variety of 4-methylene-1,3,6,7-tetraazaspiro[4.5]dec-7-en-2-one derivatives in yields of up to 88%. Additionally, in situ generated α-nitrosostyrenes are also compatible with this IEDDA reaction, producing various 4-methylene-6-oxa-1,3,7-triazaspiro[4.5]dec-7-en-2-ones. The potential utility of this method was demonstrated through a gram-scale reaction with a good yield. Particularly, a preliminary biological evaluation indicated the potential of these products for medicinal applications, exhibiting moderate to good cytotoxicity in vitro against multiple types of tumor cells.